Esophageal carcinoma is epithelially derived tumor (cancer) that occurs in the esophagus. 10,000 or more people in Japan develop esophageal carcinoma annually. The male to female ratio is about 6:1, indicating that the disease occurs more often in men. Esophageal carcinoma is the sixth most common form of cancer in men. The annual death toll ranges from 9,000 to 10,000 in Japan, accounting for 3% of total cancer cases. Esophageal carcinoma is histologically classified into esophageal squamous cell carcinoma (ESCC) and adenocarcinoma. The former is caused by canceration of mucosal epithelial cells of the esophagus, accounting for 90% or more of all the esophageal carcinoma cases. The latter is caused by canceration of Barrett esophagus cells. These cases together account for 95% or more of all the esophageal carcinoma cases.
Esophageal carcinoma even at the stage of low invasion depth frequently results in lymph node metastasis. Also the esophagus anatomically differs from other digestive system organs, having no chorionic membrane (outer membrane). Hence, the carcinoma relatively easily invades the surrounding tissues. Even now the 5-year survival rate is about 30% on average, suggesting its extremely poor prognosis among other GI cancers (gastric cancer: 60%; large-bowel cancer: 70%; liver cancer: 40%; and pancreatic cancer: 15%). Therefore, further improvement in diagnostic and therapeutic technology has been desired. As diagnostic procedures, imaging studies using esophagography, endoscopy, ultrasonic endoscopy, CT (computer tomography), PET (positron emission tomography devices), or the like and methods based on tumor markers such as SCC (squamous cell carcinoma related antigen) and CEA (carcinoembryonic antigen) are known. However, currently no promising biomarker exists at the sites of clinical practice that enables early diagnosis of the malignancy of esophageal carcinoma or a prediction of its recurrence. Meanwhile, regarding treatment, endoscopic demucosation or surgical treatment is generally carried out. In cases for which radical surgery is difficult, multidisciplinary treatment using chemotherapy or chemoradiotherapy is carried out before or after surgery. However, currently, biomarkers that enable prediction of the sensitivity to treatment do not exist. Also, clinically applied drugs for molecular target therapy, which have been revealed to be effective against breast cancer, large-bowel cancer, lung cancer and the like still do not currently exist for esophageal carcinoma.
As described above, (1) further detailed elucidation of the molecular mechanisms involved in the occurrence and development of esophageal carcinoma; (2) search for therapeutic target molecules against advanced and/or recurrent esophageal carcinoma; and (3) development of diagnostic•prognosis predictive markers for determination of a course of treatment are thought to be urgent problems.
It has been reported to date that decreased expression of Low Density Lipoprotein Receptor-Related Protein 1B (LRP1B) or deletion of the genome gene can be used for diagnosis of esophageal carcinoma (JP Patent Publication (Kokai) No. 2005-304496 A). It has also been reported that decreased expression of human Cellular Retinoic Acid Binding Protein 1 (human CRABP1) or deletion of the genome gene can be used for diagnosis of esophageal carcinoma (JP Patent Publication (Kokai) No. 2008-118866 A). However, elucidation of the molecular mechanism of ESCC has remained insufficient and further analysis therefor has been required.